Steve S. Lee

Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review.

Given the clinical and public health significance of substance disorders and the need to identify their early risk factors, we examined the association of childhood attention-deficit/hyperactivity disorder (ADHD) with substance use (nicotine, alcohol, marijuana) and abuse/dependence outcomes (nicotine, alcohol, marijuana, cocaine, other). To strengthen a potential causal inference, we meta-analyzed longitudinal studies that prospectively followed children with and without ADHD into adolescence or adulthood. Children with ADHD were significantly more likely to have ever used nicotine and other substances, but not alcohol. Children with ADHD were also more likely to develop disorders of abuse/dependence for nicotine, alcohol, marijuana, cocaine, and other substances (i.e., unspecified). Sex, age, race, publication year, sample source, and version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) used to diagnose ADHD did not significantly moderate the associations with substance outcomes that yielded heterogeneous effect sizes. These findings suggest that children with ADHD are significantly more likely to develop substance use disorders than children without ADHD and that this increased risk is robust to demographic and methodological differences that varied across the studies. Finally, few studies addressed ADHD and comorbid disruptive behavior disorders (DBD), thus preventing a formal meta-analytic review. However, we qualitatively summarize the results of these studies and conclude that comorbid DBD complicates inferences about the specificity of ADHD effects on substance use outcomes.

Psychopathology and Substance Abuse in Parents of Young Children With Attention-Deficit/Hyperactivity Disorder

OBJECTIVE To compare the prevalence of psychological disorders in parents of young children with and without attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behavior disorders (DBD). METHOD Subjects included 98 three- to seven-year-old children with DSM-IV ADHD (68 with ADHD and comorbid oppositional defiant or conduct disorder [ADHD+ODD/CD]) and 116 non-ADHD comparison children recruited in 1995-96 during the first wave of a longitudinal study. Biological mothers were administered interviews to assess ADHD and DBD in their children and mood, anxiety, and substance use disorders in themselves. In addition, they were queried about symptoms of childhood ADHD and DBD, and antisocial personality disorder in themselves and their childrens biological fathers. RESULTS Child ADHD was associated with increased rates of maternal and paternal childhood ADHD relative to comparison children. Child ADHD+ODD/CD was associated with maternal mood disorders, anxiety disorders, and stimulant/cocaine dependence, and paternal childhood DBD. Mothers of children with ADHD+ODD/CD also reported increased drinking problems in their childrens fathers. CONCLUSIONS These findings indicate that many young children with ADHD, particularly those with comorbid ODD/CD, require comprehensive services to address both their ADHD and the mental health needs of their parents.

Stimulant Medication and Substance Use Outcomes: A Meta-analysis

IMPORTANCE Psychostimulant medication is an efficacious treatment for childhood attention-deficit/hyperactivity disorder, yet controversy remains regarding potential iatrogenic effects of stimulant medication, particularly with respect to increasing susceptibility to later substance use disorders. However, stimulant treatment was previously reported to reduce the risk of substance problems. OBJECTIVE To meta-analyze the longitudinal association between treatment with stimulant medication during childhood and later substance outcomes (ie, lifetime substance use and substance abuse or dependence). DATA SOURCES Studies published between January 1980 and February 2012 were identified using review articles, PubMed, and pertinent listservs. STUDY SELECTION Studies with longitudinal designs in which medication treatment preceded the measurement of substance outcomes. DATA EXTRACTION AND SYNTHESIS Odds ratios were extracted or provided by the study authors. Odds ratios were obtained for lifetime use (ever used) and abuse or dependence status for alcohol, cocaine, marijuana, nicotine, and nonspecific drugs for 2565 participants from 15 different studies. MAIN OUTCOMES AND MEASURES Random-effects models estimated the overall association, and potential study moderators were examined. RESULTS Separate random-effects analyses were conducted for each substance outcome, with the number of studies ranging from 3 to 11 for each outcome. Results suggested comparable outcomes between children with and without medication treatment history for any substance use and abuse or dependence outcome across all substance types. CONCLUSIONS These results provide an important update and suggest that treatment of attention-deficit/hyperactivity disorder with stimulant medication neither protects nor increases the risk of later substance use disorders.

Predictors of Adolescent Functioning in Girls With Attention Deficit Hyperactivity Disorder (ADHD): The Role of Childhood ADHD, Conduct Problems, and Peer Status

Predictors of adolescent functioning were studied in an ethnically diverse sample of girls with attention deficit hyperactivity disorder (ADHD; n = 140) and age- and ethnicity-matched comparison girls (n = 88) who participated in naturalistic summer programs during childhood. Over a 5-year follow-up (sample retention = 92%; age range = 11.3–18.2 years), conduct problems were predicted by hyperactivity-impulsivity (HI) symptoms and noncompliance (NC). Academic achievement was predicted only by inattention symptoms, whereas school suspensions and expulsions were predicted by inattention symptoms (ADHD sample only), NC, and negative peer status. Substance use was predicted by NC and HI symptoms. Internalizing problems were predicted by HI symptoms, NC, and covert antisocial behavior. Finally, initial peer status was the only significant predictor of later negative social preference.

Few Girls With Childhood Attention-Deficit/Hyperactivity Disorder Show Positive Adjustment During Adolescence

Employing data from 140 prospectively followed girls with attention-deficit/hyperactivity disorder (ADHD) and 88 age- and ethnicity-matched comparison girls, we adopted a person-centered analytic approach to assess rates of adolescent positive adjustment (PA) across six domains: ADHD symptoms, externalizing symptoms, internalizing symptoms, social skills, peer acceptance, and school achievement. During adolescence, between 19.8% and 61.1% of the girls with childhood ADHD met criteria for PA when the six domains were considered independently. A total of 16.4% of the ADHD sample showed PA in at least five of six domains, versus 86.4% of the comparison girls. Results were similar when PA was examined excluding the ADHD symptom domain. Most girls did not “grow out of” the symptoms and impairments related to their ADHD.

XOMA 052, an Anti-IL-1β Monoclonal Antibody, Improves Glucose Control and β-Cell Function in the Diet-Induced Obesity Mouse Model

Recent evidence suggests that IL-1beta-mediated glucotoxicity plays a critical role in type 2 diabetes mellitus. Although previous work has shown that inhibiting IL-1beta can lead to improvements in glucose control and beta-cell function, we hypothesized that more efficient targeting of IL-1beta with a novel monoclonal antibody, XOMA 052, would reveal an effect on additional parameters affecting metabolic disease. In the diet-induced obesity model, XOMA 052 was administered to mice fed either normal or high-fat diet (HFD) for up to 19 wk. XOMA 052 was administered as a prophylactic treatment or as a therapy. Mice were analyzed for glucose tolerance, insulin tolerance, insulin secretion, and lipid profile. In addition, the pancreata were analyzed for beta-cell apoptosis, proliferation, and beta-cell mass. Mice on HFD exhibited elevated glucose and glycated hemoglobin levels, impaired glucose tolerance and insulin secretion, and elevated lipid profile, which were prevented by XOMA 052. XOMA 052 also reduced beta-cell apoptosis and increased beta-cell proliferation. XOMA 052 maintained the HFD-induced compensatory increase in beta-cell mass, while also preventing the loss in beta-cell mass seen with extended HFD feeding. Analysis of fasting insulin and glucose levels suggests that XOMA 052 prevented HFD-induced insulin resistance. These studies provide new evidence that targeting IL-1beta in vivo could improve insulin sensitivity and lead to beta-cell sparing. This is in addition to previously reported benefits on glycemic control. Taken together, the data presented suggest that XOMA 052 could be effective for treating many aspects of type 2 diabetes mellitus.

Latent Class Analysis of Antisocial Behavior: Interaction of Serotonin Transporter Genotype and Maltreatment

To improve understanding about genetic and environmental influences on antisocial behavior (ASB), we tested the association of the 44-base pair polymorphism of the serotonin transporter gene (5-HTTLPR) and maltreatment using latent class analysis in 2,488 boys and girls from Wave 1 of the National Longitudinal Study of Adolescent Health. In boys, ASB was defined by three classes (Exclusive Covert, Mixed Covert and Overt, and No Problems) whereas in girls, ASB was defined by two classes (Exclusive Covert, No Problems). In boys, 5-HTTLPR and maltreatment were not significantly related to ASB. However, in girls, maltreatment, but not 5-HTTLPR, was significantly associated with ASB. A significant interaction between 5-HTTLPR and maltreatment was also observed, where maltreated girls homozygous for the short allele were 12 times more likely to be classified in the Exclusive Covert group than in the No Problems group. Structural differences in the latent structure of ASB at Wave 2 and Wave 3 prevented repeat LCA modeling. However, using counts of ASB, 5-HTTLPR, maltreatment, and its interaction were unrelated to overt and covert ASB at Wave 2 and only maltreatment was related to covert ASB at Wave 3. We discuss these findings within the context of sex differences in ASB and relevant models of gene-environment interplay across developmental periods.

Association of maternal dopamine transporter genotype with negative parenting: evidence for gene x environment interaction with child disruptive behavior

Although maternal parenting is central to child development, little is known about the interplay between molecular genetic and environmental factors that influence parenting. We tested the association of the 40-bp variable number tandem repeat polymorphism of the dopamine transporter (DAT1; SLC6A3) gene with three dimensions of observed maternal parenting behavior (positive parenting, negative parenting and total maternal commands). A significant nonadditive association was found between maternal DAT1 genotype and both negative parenting and total commands during a structured mother–child interaction task, even after controlling demographic factors, maternal psychopathology and disruptive child behavior during the task. Furthermore, the association between maternal DAT1 genotype and negative parenting was significantly stronger among mothers whose children were highly disruptive during the mother–child interaction task, suggesting a gene–environment interaction.

Severity of Adolescent Delinquency Among Boys With and Without Attention Deficit Hyperactivity Disorder: Predictions From Early Antisocial Behavior and Peer Status

This study evaluated predictors of adolescent delinquency severity (11 to 17 years of age) among a diverse group of preadolescent boys with attention deficit hyperactivity disorder (ADHD; n = 100) and age-matched comparison boys (n = 75). During childhood, baseline assessments yielded diagnostic information, and naturalistic summer programs provided multimethod measures of overt aggression, covert antisocial behavior (ASB), and peer status. Five years later, multi-informant measures of ASB and delinquency were gathered and independently rated. Baseline ADHD, overt aggression, and peer status were not significantly related to adolescent delinquency severity. Observed noncompliance and an objective measure of covert ASB each independently predicted delinquency. Covert ASB predicted delinquency severity more strongly for comparison boys than for probands.

Are there sex differences in the predictive validity of DSM-IV ADHD among younger children?

We assessed the predictive validity of attention-deficit/hyperactivity disorder (ADHD) in 20 girls and 98 boys who met the Diagnostic and Statistical Manual for Mental Disorders (4th ed., American Psychiatric Association, 1994) criteria for ADHD at 4 to 6 years of age compared to 24 female and 102 male comparison children. Over the next 8 years, both girls and boys who met criteria for ADHD in Year 1 exhibited more ADHD symptoms and impairment than same-sex comparison children. Effect sizes were consistently large, indicating that the diagnosis of ADHD at 4 to 6 years of age has predictive validity for both sexes. Both girls and boys with ADHD in Year 1 also exhibited higher levels of symptoms of conduct disorder, major depression, and anxiety disorders in early adolescence than same-sex comparison children, controlling levels of the same symptoms in Year 1. This indicates both substantial homotypic and heterotypic continuity for ADHD in both sexes, but significant interactions with time indicated that childhood ADHD predicts more steeply rising symptoms of anxiety and depression during early adolescence in girls than in boys.